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https://www.readbyqxmd.com/read/28449103/novel-degenerative-and-developmental-defects-in-a-zebrafish-model-of-mucolipidosis-type-iv
#1
Huiqing Li, Wuhong Pei, Sivia Vergarajauregui, Patricia M Zerfas, Nina Raben, Shawn M Burgess, Rosa Puertollano
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family. In this study we used genome editing to knockout the two mcoln1 genes present in Dario rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28448473/transcriptomic-analysis-of-calcium-remodeling-in-colorectal-cancer
#2
Enrique Pérez-Riesgo, Lucía G Gutiérrez, Daniel Ubierna, Alberto Acedo, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Colorectal cancer (CRC) cells undergo the remodeling of intracellular Ca(2+) homeostasis, which contributes to cancer hallmarks such as enhanced proliferation, invasion and survival. Ca(2+) remodeling includes critical changes in store-operated Ca(2+) entry (SOCE) and Ca(2+) store content. Some changes have been investigated at the molecular level. However, since nearly 100 genes are involved in intracellular Ca(2+) transport, a comprehensive view of Ca(2+) remodeling in CRC is lacking. We have used Next Generation Sequencing (NGS) to investigate differences in expression of 77 selected gene transcripts involved in intracellular Ca(2+) transport in CRC...
April 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#3
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28437833/transient-receptor-potential-trp-channels-and-exercise-associated-muscle-cramping-eamc-a-tale-of-multiple-complexities
#4
EDITORIAL
M P Schwellnus, M D Hoffman
No abstract text is available yet for this article.
April 24, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28432033/lipids-as-central-modulators-of-sensory-trp-channels
#5
REVIEW
Maria Grazia Ciardo, Antonio Ferrer-Montiel
The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28430359/sulfur-containing-gaseous-signal-molecules-ion-channels-and-cardiovascular-diseases
#6
REVIEW
Wen Yu, Hongfang Jin, Chaoshu Tang, Junbao Du, Zhiren Zhang
Sulfur-containing gaseous signal molecules including hydrogen sulfide (H2 S) and sulfur dioxide (SO2 ) were previously recognized as toxic gases. However, extensive studies have revealed that they can be generated in the cardiovascular system via a sulfur-containing amino acid metabolic pathway, playing an important part in cardiovascular physiology and pathophysiology. Ion channels are pore-forming membrane proteins present in the membrane of all biological cells; functions include establishing a resting membrane potential and controlling action potentials and other electrical signals by conducting ions across the cell membrane...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28424587/interactions-of-the-mechanosensitive-channels-with-extracellular-matrix-integrins-and-cytoskeletal-network-in-osmosensation
#7
REVIEW
Runsheng Jiao, Dan Cui, Stephani C Wang, Dongyang Li, Yu-Feng Wang
Life is maintained in a sea water-like internal environment. The homeostasis of this environment is dependent on osmosensory system translation of hydromineral information into osmotic regulatory machinery at system, tissue and cell levels. In the osmosensation, hydromineral information can be converted into cellular reactions through osmoreceptors, which changes thirst and drinking, secretion of antidiuretic vasopressin (VP), reabsorption of water and salt in the kidneys at systemic level as well as cellular metabolic activity and survival status at tissue level...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28416581/trp-channels-in-brown-and-white-adipogenesis-from-human-progenitors-new-therapeutic-targets-and-the-caveats-associated-with-the-common-antibiotic-streptomycin
#8
Anna Goralczyk, Marc van Vijven, Mathilde Koch, Cedric Badowski, M Shabeer Yassin, Sue-Anne Toh, Asim Shabbir, Alfredo Franco-Obregón, Michael Raghunath
Transient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific...
April 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28416203/the-s4-s5-linker-gearbox-of-trp-channel-gating
#9
REVIEW
Laura Hofmann, Hongmei Wang, Wang Zheng, Stephan E Philipp, Patricia Hidalgo, Adolfo Cavalié, Xing-Zhen Chen, Andreas Beck, Veit Flockerzi
Transient receptor potential (TRP) channels are cation channels which participate in a wide variety of physiological processes in organisms ranging from fungi to humans. They fulfill roles in body homeostasis, are sensors for noxious chemicals and temperature in the mammalian somatosensory system and are activated by light stimulated phospholipase C activity in Drosophila or by hypertonicity in yeast. The transmembrane topology of TRP channels is similar to that of voltage-gated cation channels. TRP proteins assemble as tetramers with each subunit containing six transmembrane helices (S1-S6) and intracellular N- and C-termini...
April 4, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28409923/the-catalase-activity-of-catalase-peroxidases-is-modulated-by-changes-in-the-pka-of-the-distal-histidine
#10
Miguel Machuqueiro, Bruno Victor, Jacek Switala, Jacylyn Villanueva, Carme Rovira, Ignacio Fita, Peter C Loewen
The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an associated mobile Arg is essential for catalase activity in catalase-peroxidases. In addition, acidic residues in the entrance channel, in particular an Asp and a Glu ∼7 and ∼15 Å, respectively, from the heme, significantly enhance catalase activity. The mechanism by which these channel carboxylates influence catalase activity is the focus of this work. Seventeen new variants with fewer and additional acidic residues have been constructed and characterized structurally and for enzymatic activity, revealing that their effect on activity is roughly inversely proportional to their distance from the heme and adduct, suggesting that the electrostatic potential of the heme cavity may be affected...
April 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28395140/pyrazolopyrimidines-as-potent-stimulators-for-transient-receptor-potential-canonical-3-6-7-channels
#11
Chunrong Qu, Mingmin Ding, Yingmin Zhu, Yungang Lu, Juan Du, Melissa Miller, Jinbin Tian, Jinmei Zhu, Jian Xu, Meng Wen, Aga Er-Bu, Jule Wang, Yuling Xiao, Meng Wu, Owen B McManus, Min Li, Jilin Wu, Huai-Rong Luo, Zhengyu Cao, Bing Shen, Hongbo Wang, Michael X Zhu, Xuechuan Hong
Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approach, a lead compound with the pyrazolopyrimidine skeleton was identified as a TRPC6 agonist. Synthetic schemes for the lead and its analogues were established, and structural-activity relationship studies were carried out...
April 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28385695/transient-receptor-potential-ion-channel-function-in-sensory-transduction-and-cellular-signaling-cascades-underlying-visceral-hypersensitivity
#12
Dafne Balemans, Guy E Boeckxstaens, Karel Talavera, Mira M Wouters
Visceral hypersensitivity is an important mechanism underlying increased abdominal pain perception in functional gastrointestinal disorders (FGID) including functional dyspepsia, irritable bowel syndrome (IBS) and inflammatory bowel disease in remission. Although the exact pathophysiological mechanisms are poorly understood, recent studies described upregulation and altered functions of nociceptors and their signaling pathways in aberrant visceral nociception, in particular the transient receptor potential (TRP) channel family...
April 6, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28377424/the-ca2-permeable-cation-trpv3-channel-an-emerging-pivotal-target-for-itch-and-skin-diseases
#13
Gongxin Wang, Kewei Wang
Temperature-sensitive transient receptor potential (thermo-TRP) channels such as TRPA1 and TRPV1 have been indicated as downstream ion channel targets in transduction of itch. As a member of thermos-TRPs, Ca2+-permeable nonselective cation TRPV3 channels are expressed abundantly in the skin keratinocytes. Recent identification of gain-of-function mutations of human TRPV3 from patients with Olmsted Syndrome characterized by severe itching and palmoplantar and periorificial keratoderma unveils its crucial role in chronic itch and skin diseases...
April 4, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28374795/a-gate-hinge-controls-the-epithelial-calcium-channel-trpv5
#14
Jenny van der Wijst, Elizabeth H Leunissen, Maxime G Blanchard, Hanka Venselaar, Sjoerd Verkaart, Candice E Paulsen, René J Bindels, Joost G Hoenderop
TRPV5 is unique within the large TRP channel family for displaying a high Ca(2+) selectivity together with Ca(2+)-dependent inactivation. Our study aims to uncover novel insights into channel gating through in-depth structure-function analysis. We identify an exceptional tryptophan (W583) at the terminus of the intracellular pore that is unique for TRPV5 (and TRPV6). A combination of site-directed mutagenesis, biochemical and electrophysiological analysis, together with homology modeling, demonstrates that W583 is part of the gate for Ca(2+) permeation...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373693/trpv1-temperature-activation-is-specifically-sensitive-to-strong-decreases-in-amino-acid-hydrophobicity
#15
Jason O Sosa-Pagán, Edwin S Iversen, Jörg Grandl
Several transient receptor potential (TRP) ion channels can be directly activated by hot or cold temperature with high sensitivity. However, the structures and molecular mechanism giving rise to their high temperature sensitivity are not fully understood. One hypothesized mechanism assumes that temperature activation is driven by the exposure of hydrophobic residues to solvent. This mechanism further predicts that residues are exposed to solvent in a coordinated fashion, but without necessarily being located in close proximity to each other...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28364279/trpv1-and-trpa1-in-cutaneous-neurogenic-and-chronic-inflammation-pro-inflammatory-response-induced-by-their-activation-and-their-sensitization
#16
REVIEW
Olivier Gouin, Killian L'Herondelle, Nicolas Lebonvallet, Christelle Le Gall-Ianotto, Mehdi Sakka, Virginie Buhé, Emmanuelle Plée-Gautier, Jean-Luc Carré, Luc Lefeuvre, Laurent Misery, Raphaele Le Garrec
Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli...
March 31, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28349862/dopamine-signaling-tunes-spatial-pattern-selectivity-in-c-elegans
#17
Bicheng Han, Yongming Dong, Lin Zhang, Yan Liu, Ithai Rabinowitch, Jihong Bai
Animals with complex brains can discriminate the spatial arrangement of physical features in the environment. It is unknown whether such sensitivity to spatial patterns can be accomplished in simpler nervous systems that lack long-range sensory modalities such as vision and hearing. Here we show that the nematode Caenorhabditis elegans can discriminate spatial patterns in its surroundings, despite having a nervous system of only 302 neurons. This spatial pattern selectivity requires touch-dependent dopamine signaling, including the mechanosensory TRP-4 channel in dopaminergic neurons and the D2-like dopamine receptor DOP-3...
March 28, 2017: ELife
https://www.readbyqxmd.com/read/28349093/regulation-of-thermotrps-by-lipids
#18
REVIEW
Sara L Morales-Lázaro, Luis Lemus, Tamara Rosenbaum
The family of Transient Receptor Potential (TRP) ion channels is constituted by 7 subfamilies among which are those that respond to temperature, the thermoTRPs. These channels are versatile molecules of a polymodal nature that have been shown to be modulated in various fashions by molecules of a lipidic nature. Some of these molecules interact directly with the channels on specific regions of their structures and some of these promote changes in membrane fluidity or modify their gating properties in response to their agonists...
2017: Temperature: Multidisciplinary Biomedical Journal
https://www.readbyqxmd.com/read/28346371/modulation-of-trp-channel-activity-by-hydroxylation-and-its-therapeutic-potential
#19
REVIEW
Yagnesh Nagarajan, Grigori Y Rychkov, Daniel J Peet
Two transient receptor potential (TRP) channels-TRPA1 and TRPV3-are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28340295/response-of-catalase-of-the-mouse-primary-hepatocytes-to-sodium-dodecylbenzenesulfonate-and-the-underlying-molecular-mechanisms
#20
Jing Wang, Jiaxi Wang, Lu Zhang, Rutao Liu, Wansong Zong
This study investigated the adverse effects of sodium dodecylbenzenesulfonates (SDBS) on mouse primary hepatocytes by conducting cell viability, intracellular oxidative stress level, and catalase (CAT) activity assays. It was shown that SDBS altered CAT activities, triggered oxidative stress, and thus exhibited cytotoxicity to the hepatocytes. Both the stimulation of intracellular CAT production and the inhibition of molecular CAT activity contributed to intracellular CAT activity change. Molecular mechanisms underlying CAT activity inhibition and structural changes were explored by isothermal titration calorimetry, multispectroscopy, and molecular docking studies...
March 29, 2017: Journal of Agricultural and Food Chemistry
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